Perspectives for Computer Modeling in the Study of T Cell Activation
Overview
Molecular Biology
Affiliations
The T cell receptor (TCR) is responsible for discriminating between self- and foreign-derived peptides, translating minute differences in amino-acid sequence into large differences in response. Because of the great variability in the TCR and its ligands, activation of T cells by foreign peptides is a quantitative process, dependent on a mix of upstream signals and downstream integration. Accordingly, quantitative data and computational models have shed light on many important aspects of this process: molecular noise in ligand recognition, spatial dynamics in T cell-APC (antigen presenting cell) interactions, graded versus all-or-none decision making by the TCR apparatus, mechanisms of peptide antagonism and synergism, and the tunability and robustness of activation thresholds. Though diverse in their formalism, these studies together paint a picture of how modeling has shaped and will continue to shape understanding of T cell immunobiology.
Neve-Oz Y, Sherman E, Raveh B Front Immunol. 2024; 15:1412221.
PMID: 39524449 PMC: 11543436. DOI: 10.3389/fimmu.2024.1412221.
A Rapid Translational Immune Response Program in CD8 Memory T Lymphocytes.
Salloum D, Singh K, Davidson N, Cao L, Kuo D, Sanghvi V J Immunol. 2022; 209(6):1189-1199.
PMID: 36002234 PMC: 9492650. DOI: 10.4049/jimmunol.2100537.
Regulation of T Helper Cell Fate by TCR Signal Strength.
Bhattacharyya N, Feng C Front Immunol. 2020; 11:624.
PMID: 32508803 PMC: 7248325. DOI: 10.3389/fimmu.2020.00624.
Experimental and theoretical bases for mechanisms of antigen discrimination by T cells.
Kajita M, Yokota R, Aihara K, Kobayashi T Biophysics (Nagoya-shi). 2016; 11:85-92.
PMID: 27493520 PMC: 4736787. DOI: 10.2142/biophysics.11.85.
Affinity and dose of TCR engagement yield proportional enhancer and gene activity in CD4+ T cells.
Allison K, Sajti E, Collier J, Gosselin D, Troutman T, Stone E Elife. 2016; 5.
PMID: 27376549 PMC: 4931909. DOI: 10.7554/eLife.10134.